The proposed research will further delineate the roles of the alpha and beta cells by endeavoring to answer the following questions: 1) Do the alpha and/or beta cells mediate carbohydrate-induced hypolipemia? The effect of concurrent and antecedent carbohydrate intake upon the insulin and glucagon responses to noncarbohydrate meals will be studied and the effect of endogenous hyperglucagonemia upon endogenous triglyceride levels determined; 2) Do the alpha and beta cells mediate the metabolic effects of anabolic and catabolic steroids? Basal and amino acid stimulated levels of insulin and glucagon will be compared in conscious dogs during chronic androgen administration and, in another group of dogs during normal, Cushingoid, and Addisonian levels of cortisol; 3) Is endogenous insulin secretion important in protecting against hyperkalemia during intravenous potassium therapy? This will be carefully examined in patients receiving such treatment and the possibility that the chronically potassium-depleted beta cell is functionally incapable of adequate protection against hyperkalemia will be explored in dogs and in rats by in vivo and in vitro functional and morphologic techniques; 4) What is the pathophysiology of the alpha cell derangement in experimental and human genetic diabetes? The ability of insulin to restore to normal the deranged alpha cell function of genetic diabetes will be carefully examined, alpha cell function in prediabetes examined, human nondiabetic and diabetic islets of Langerhans of beating heart cadavers compared. 5) What is the physiologic contribution of glucagon in health and its pathophysiologic contribution in diabetes to nutrient homeostasis? Somatostatin will be used as a glucagon-suppressing agent. 6) What is the physiologic role or roles of enteroglucagon? An attempt to purify, synthesize and characterize polypeptides will be made. 7) Can beta cell multiplication in tissue culture be increased by methods which might someday have therapeutic application in human diabetes?